A. Field of the Invention
The present invention relates to biocompatible glass compositions, and more particularly to alkali-free compositions produced by a sol-gel process.
B. Description of the Prior Art
Bioactivity is a unique property associated with the ability of a synthetic material to bond with living tissue. All materials implanted in vivo elicit a response from the surrounding tissue. Four types of response are possible: (i) if the material is toxic, the tissue dies; (ii) if the material is nontoxic and dissolves, the surrounding tissue replaces it; (iii) if the material is nontoxic and biologically inactive, a fibrous tissue capsule of variable thickness forms; and (iv) if the material is nontoxic and biologically active, an interfacial bond forms. Bioactive materials are those which produce the fourth type of response.
Three key compositional features distinguish bioactive glasses from traditional soda-lime-silica glasses and provide the driving force for bonding with living tissues. Conventional bioactive glasses, which are well-characterized in the art, typically contain less than 60 mole percent SiO.sub.2, high Na.sub.2 O and CaO content (20-25% each), and a high molar ratio of calcium to phosphorus (ranging around five). When such glasses are exposed to water or body fluids, several key reactions occur. The first is cation exchange, wherein interstitial Na.sup.+1 and Ca.sup.+2 ions from the glass are replaced by protons from solution, forming surface silanol groups and nonstoichiometric hydrogen-bonded complexes: ##STR1##
This cation exchange also increases the hydroxyl concentration of the solution, leading to attack of the fully dense silica glass network to produce additional silanol groups and controlled interfacial dissolution: EQU Si--O--Si+H.sup.+ OH.sup.- .fwdarw.Si--OH+HO--Si [2]
As the interfacial pH becomes more alkaline and the concentration of hydrolyzed surface silanol groups increases, the conformational dynamics attending high numbers of proximal silanol groups, combined with the absence of interstitial ions, cause these groups to repolymerize into a silica-rich surface layer: EQU Si--OH+HO--Si.fwdarw.Si--O--Si+H.sub.2 O [3]
Another consequence of alkaline pH at the glass-solution interface is crystallization into a mixed hydroxyl-apatite phase of the CaO and P.sub.2 O.sub.5 that were released into solution during the network dissolution of Equation 2. This takes place on the SiO.sub.2 surface. The hydroxyapatite crystallites nucleate and bond to interfacial metabolites such as mucopolysaccharides, collagen and glycoproteins. It appears that incorporation of organic biological constituents within the growing hydroxyapatite- and SiO.sub.2 -rich layers triggers bonding to living tissues characteristic of bioactivity.
Currently, bioactive powders are produced by conventional processing techniques well-known in the art. The various constituents (e.g., reagent-grade Na.sub.2 CO.sub.3, CaCO.sub.3, P.sub.2 O.sub.5 and SiO.sub.2) are usually mixed in a suitable mixing device such as a rolling mill, and then heated in a platinum crucible to a temperature (generally between 1250 and 1400 degrees Centigrade) sufficient to cause the particles to melt and coalesce. See, e.g., U.S. Pat. No. 4,775,646; Ogino, Ohuchi & Hench, Compositional Dependence of the Formation of Calcium Phosphate Films on Bioglass, 14 J. Biomed. Mat. Res. 55, 56 (1980). The use of such high temperatures and specialized equipment results in significant production costs.
Conventional bioactive glasses suffer from other shortcomings in addition to high cost. These compositions tend to require an alkali metal oxide such as Na.sub.2 O to serve as a flux or aid in melting or homogenization. However, the presence of alkali metal oxide ions results in a high pH at the interface between the glass and surrounding fluid or tissue; in vivo, this can induce inflammation. Furthermore, the rate of tissue repair, which drives the interfacial tissue-glass bonding promoted by bioactive material, tends to vary within a narrow pH range. If the surrounding environment grows too acidic or alkaline, repair shuts down, and interfacial bonding is defeated. Consequently, high rates of bioactivity (as measured by surface hydroxyapatite accretion) tend to be associated with significant local pH changes due to the release of alkali metal oxide ions, and have heretofore been avoided.
Conventional glasses also tend to be difficult to mix to homogeneity, a criterion that holds great importance for quality control of materials intended for implantation in the body. This is due to the relatively large grain size of the glass precursors, which generally measure approximately 10 to 1000 microns in diameter. It is difficult to obtain "molecular scale" mixing, i.e., homogeneity at the molecular level, using ordinary mixing techniques, such as stirring of the relatively viscous silicate melts.
Finally, for reasons discussed in more detail below, current bioactive powders cannot be prepared with a SiO.sub.2 content greater than 60 mole percent. This limitation imposes a significant constraint on the producer's ability to tailor the material for a particular situation. It can be highly useful, for example, to vary the rate of hydroxyapatite formation, which is dependent upon SiO.sub.2 content. As discussed above, the rate of metabolic tissue repair determines how quickly bonding between the tissue and a bioactive material can progress. Therefore, compatibility between the bioactive material and the surrounding tissue will be maximized when the material's bioactivity rate--that is, the speed with which hydroxyapatite is produced--matches the body's metabolic repair rate. However, an individual's repair rate can vary with age and disease state, among other factors, rendering identification of a single, ideal bioactivity rate impossible.
The SiO.sub.2 level also determines the thermal expansion coefficient and elastic modulus of the glass. Particularly in the case of porous compositions, the ability to coat the glass onto a strong substrate (e.g., metal) significantly increases the range of clinical applications to which the glass will be amenable. Such coating is most conveniently accomplished when the thermal expansion coefficient of the glass matches that of the substrate, and restrictions on SiO.sub.2 variation diminish the range of coefficients that may be achieved. Similarly, particular values or ranges for the elastic modulus can also be important in certain clinical applications (such as avoiding stress shielding of the repair of long bones and joints), rendering some glass compositions unsuitable if the SiO.sub.2 level cannot be adjusted sufficiently.